Modulation of the NF-kappa B Pathway by Virally Encoded Death Effector Domains-Containing Proteins

Oncogene. 1999 Oct 14;18(42):5738-46. doi: 10.1038/sj.onc.1202976.

Abstract

Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the ability of blocking cell death induced by DD-containing receptors. We provide evidence that vFLIPs can also modulate the NF-kappaB pathway and physically interact with several signaling proteins, such as the TRAFs, RIP, NIK and the IKKs. Modulation of the NF-kappaB pathway may play a role in the natural history of infection by these viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens, Viral
  • Apoptosis / physiology*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Cell Line
  • Herpesvirus 8, Human / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Mice
  • NF-kappa B / metabolism*
  • Nuclear Proteins / physiology
  • Peptide Fragments / physiology*
  • Phosphotransferases / metabolism
  • Proteins / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / physiology
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Cells, Cultured
  • Viral Proteins / physiology*

Substances

  • Antigens, Viral
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Cflar protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Peptide Fragments
  • Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNFRSF10B protein, human
  • Tnfrsf10b protein, mouse
  • Viral Proteins
  • latency-associated nuclear antigen
  • Phosphotransferases
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases